Synthesis, SAR and molecular docking studies of benzo[d]thiazole-hydrazones as potential antibacterial and antifungal agents.

A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole. A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring. The electron donating (OH and OCH3) groups presented in the analogues, increase the antibacterial activity (except compound 12), interestingly, while the electron withdrawing (Cl, NO2, F and Br) groups increase the antifungal activity (except compound 19 and 20). In addition, analogues containing thiophene (28) and indole (30) showed good antimicrobial activities. Whereas, aliphatic analogues (24-26) shown no activities in both bacterial and fungal stains even in high concentrations (100µg/mL). Molecular docking studies were performed for all the synthesized compounds of which compounds 11, 19 and 20 showed the highest glide G-score.

Synthesis of benzo[d]thiazole-hydrazone analogues: molecular docking and SAR studies of potential H+/K+ ATPase inhibitors and anti-inflammatory agents.

A series of new benzo[d]thiazole-hydrazones were synthesized and characterized by analytical and spectroscopic techniques. All the compounds were screened for their in vitro inhibition of H+/K+ ATPase and anti-inflammatory effects. The results revealed that compounds 6-8, 13-15, 18-20, 22, 23 and 27-30 displayed excellent inhibitory activity against H+/K+ ATPase, and their IC50 values were lower than those of the standard compound omeprazole. Compounds 2-5, 9-12, 28 and 30 exhibited better anti-inflammatory activity in comparison to the standard compound indomethacin. Studies of the structure-activity relationship (SAR) showed that electron-donating groups (OH and OCH3) favored inhibitory activity against H+/K+ ATPase, whereas electron-withdrawing groups (F, Cl, Br and NO2) favored anti-inflammatory activity, and derivatives with both electron-donating (OH and OCH3) and electron-withdrawing (Br) groups (16-18) displayed reasonable activity, whereas aliphatic analogues (24-26) exhibited less activity and heterocyclic analogues (27-30) displayed moderate activity in both biological studies. Molecular docking studies were performed for all the synthesized compounds, among which compounds 19 and 20 exhibited the highest docking scores for inhibitory activity against H+/K+ ATPase, whereas compounds 10 and 12 displayed the highest docking scores for anti-inflammatory activity.

Synthesis and molecular docking studies of xanthone attached amino acids as potential antimicrobial and anti-inflammatory agents.

A series of novel xanthone conjugated amino acids were synthesised and characterised by analytical and spectroscopic methods. All the synthesized analogues (2-23) were screened for their in vitro antimicrobial and anti-inflammatory activities. Compounds 7, 8, 9, 12, 18, 19, 20, 21 and 23 showed excellent antimicrobial activities compared to antibacterial and antifungal reference drugs gentamicin and bavistin, respectively. Compounds 7-12 and 18-23 showed good anti-inflammatory activity compared to a standard drug, indomethacin. The preliminary structure-activity relationship revealed that tryptophan, tyrosine, phenylalanine, proline and cysteine conjugated compounds showed excellent antimicrobial and anti-inflammatory activities. This may be explained by the contribution of aromaticity and hydrophobicity of amino acids. Molecular docking studies were performed for all the synthesised compounds, among which compounds 20, 21 and 23 showed the highest docking scores for antimicrobial activity while compounds 9, 20 and 22 showed the highest docking scores for anti-inflammatory activity. Different amino acids conjugated xanthone derivatives were synthesized and evaluated for their in vitro biological activities. The conjugation was found to play a major role in improving the biological activities of those compounds.